a. Field of Invention
This invention relates to a novel and useful process for preparing 1,4:3,6-dianhydro-D-glucitol 2-nitrate.
B. Description of the Prior Art
1,4:3,6-Dianhydro-D-glucitol 2-nitrate, commonly called isosorbide-2-nitrate, has been established to be a useful compound having coronary vasodilator activity, see, for example, the report by R. L. Wendt, J. Pharmacol. Exp. Ther., 180, 732(1972).
1,4:3,6-Dianhydro-D-glucitol 2-nitrate has been prepared by the direct nitration of 1,4:3,6-dianhydro-D-glucitol by I. G. Csizmadia and L. D. Hayward, Photochem. Photobiol., 4, 657(1965). The 1,4:3,6-dianhydro-D-glucitol 2-nitrate is produced by the process of the latter reference as a minor constituent in a mixture of nitrates and has to be isolated from the mixture by column chromatography. The yield thereby obtained is very low and the method of isolation is time consuming and expensive so that use of this method as a commercial process is economically prohibitive. In addition, this prior art method also produces substantial quantities of 1,4:3,6-dianhydro-D-glucitol 2,5-dinitrate. This dinitrate, in contrast to the mononitrates, has potential explosive properties. In contradistintion, the process of this invention produces 1,4:3,6-dianhydro-D-glucitol 2-nitrate as the major component without any hazardous amounts of the dinitrate being formed. Moreover, the 1,4:3,6-dianhydro-D-glucitol 2-nitrate, being the principal reaction product in the process of this invention, is isolated directly in high purity by a simple crystallization of the crude reaction product from a suitable solvent. Thus, the process of this invention produces 1,4:3,6-dianhydro-D-glucitol 2-nitrate in an economically feasable method, without formation of any of the hazardous dinitrate, and the isolation and purification of the 2-nitrate by crystallization avoids the need for chromatography or other protracted and expensive purification procedures.